title: Panax notoginseng saponins promote endothelial progenitor cell mobilization and attenuate atherosclerotic lesions in apolipoprotein E knockout mice.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) derived from the bone marrow (BM) play a key role in the homeostasis of vascular repair by enhanced reendothelialization. Panax notoginseng saponins (PNS), a highly valued traditional Chinese medicine, has been shown to reduce morbidity and mortality from coronary artery disease. The present research was designed to explore the contribution of progenitor cells to the progression of atherosclerotic plaques and the possible modulatory role of PNS in this process.
  
  
  METHODS
  PNS (60 or 120 mg/kg via intraperitoneal injection) was administered over 8 weeks in apolipoprotein E knockout mice on an atherogenic diet. The sizes and histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and peripheral blood were analyzed. The expression of chemokine stromal cell-derived factor 1α (SDF-1α) and its receptor, CXCR4, was monitored as well.
  
  
  RESULTS
  PNS significantly reduced the lesion area and intima-to-media ratio compared to vehicle treatment. PNS also augmented endothelialization and reduced the smooth muscle cell (SMCs) content of the lesions. The number of c-kit and sca-1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor cells were significantly increased in the BM and the peripheral blood of the PNS-treated groups. PNS treatment increased the plasma levels of SDF-1α and SCF as well as the BM levels of matrix metalloproteinase-9 (MMP-9). Moreover, the mRNA levels of SDF-1α and protein levels of CXCR4 were both increased in the BM of mice treated with PNS, while SDF-1α expression decreased.
  
  
  CONCLUSIONS
  PNS reduce the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilization. SDF-1α-CXCR4 interactions and the possible modulatory role of PNS in this process may contribute to the increased progenitor cell mobilization.
authors.affiliation: Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.forename: Haigang
authors.initials: H
authors.lastname: Zhang
authors.forename: Dayan
authors.initials: D
authors.lastname: Cao
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053723:Panax notoginseng / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D001057:Apolipoproteins E; D012503:Saponins